Elsevier

Heart Rhythm

Volume 6, Issue 11, Supplement, November 2009, Pages S68-S75
Heart Rhythm

Heart rate, autonomic markers, and cardiac mortality

https://doi.org/10.1016/j.hrthm.2009.07.017Get rights and content

Heart rate is a precisely regulated variable, which plays a critical role in health and disease. Numerous epidemiologic studies and large post-myocardial infarction trials have provided evidence that elevated resting heart rate is an independent risk factor for cardiac mortality. This body of knowledge has prompted the development and evaluation of negative chronotropic agents, prototypically the If inhibitor Ivabradine. The present review addresses several fundamental questions: (1) How is heart rate regulated at the integrative, cellular, and molecular levels? (2) How are autonomic tone and reflexes measured clinically, and what is the prognostic utility of these parameters? (3) What mechanisms are responsible for the cardiovascular pathology associated with elevated heart rates? (4) Does reducing heart rate independent of effects on other factors protect against cardiovascular events?

Section snippets

How is heart rate regulated?

Control of the sinoatrial node is achieved through both intrinsic and extrinsic mechanisms. Its intrinsic regulation is determined by the If pacemaker current, which establishes the slope of spontaneous diastolic depolarization. Sinoatrial node depolarization has been attributed to a “voltage clock” regulated by voltage-sensitive membrane currents, particularly the hyperpolarization-activated pacemaker current, If, which is regulated by cyclic adenosine monophosphate (cAMP). Recent evidence

How are autonomic tone and reflexes measured clinically?

Numerous techniques developed to evaluate autonomic function in health and disease have been extensively reviewed.7, 21 They can be classified in two general categories as measures largely of tonic activity (heart rate, heart rate variability [HRV]7, 21, 22) or reflex baroreceptor function (baroreceptor sensitivity [BRS]22, 23 or heart rate turbulence [HRT]3, 24). Parameters that reflect the combined influence of autonomic tone and reflexes and hemodynamic factors have also been explored. These

HRV

Autonomic nervous system tone has been studied in human subjects primarily by analyzing HRV. The underlying principle is that the pattern of beat-to-beat control of the sinoatrial node reflects autonomic influences on the cardiovascular system. Parasympathetic influences exert a unique imprimatur through rapid dynamic control by release of acetylcholine, which affects muscarinic receptors, and are therefore reflected in the high-frequency component of HRV. Sympathetic nerve activity, through

BRS

The classic studies by Schwartz and coworkers23 focused attention on the importance of baroreceptor function in determining susceptibility to life-threatening arrhythmias associated with myocardial ischemia and infarction. They demonstrated that during exercise, canines with more powerful baroreflex responses were less vulnerable to ventricular fibrillation during myocardial ischemia superimposed on prior myocardial infarction. The protective effect of the baroreceptor mechanism has been

HRT

BRS can also be monitored noninvasively from routine ambulatory electrocardiograms using the tool of HRT, which measures heart rate fluctuations after a single ventricular premature beat (VPB), which reflect the fall and recovery of blood pressure.3 These reactions of the cardiovascular system to a VPB are direct functions of baroreceptor responsiveness, as reflex activation of the vagus nerve controls the pattern of sinus rhythm. In low-risk patients, sinus rhythm exhibits a characteristic

Heart rate recovery

Heart rate recovery after exercise, another marker of vagus nerve responsiveness, has proved to be highly predictive of cardiovascular mortality and sudden cardiac death in a variety of relatively low-risk cohorts including asymptomatic individuals.1, 26, 27 The reduction in heart rate during the first 30–60 seconds after exercise appears to be caused principally by reactivation of the parasympathetic nervous system but subsequently by withdrawal of sympathetic tone.25 However, because the

What mechanisms mediate the cardiovascular pathology associated with elevated heart rates?

Elevated heart rates can influence the development of cardiovascular disease through a multitude of actions that can be classified both as long-term and acute effects. The underlying pathophysiologic mechanisms have been reviewed by the Heart Rate Working Group.2 The long-term consequences of elevated heart rate can be subtle and insidious. Over the course of a lifetime, elevations in heart rate catalyze the atherosclerotic processes30 and associated increases in arterial stiffness through

Does reducing heart rate independent of other factors protect against cardiovascular events?

Because of mounting epidemiological evidence and plausible physiologic mechanisms for a cardioprotective role of lowered resting heart rate, in recent years there has been strong interest in using heart rate as a therapeutic target to reduce the risk for cardiovascular mortality and sudden cardiac death. Multiple favorable and unfavorable countervailing effects are likely to play a role in the outcome (Table 1). A net benefit of pharmacological interventions that reduce heart rate is documented

Conclusions

Heart rate is a pivotal variable that is precisely regulated in health but disrupted in disease. The influence of altered heart rate is multifactorial, affecting the progression of coronary vascular and myocardial disease. Whereas there is evidence that elevated heart rate is prognostic of cardiovascular events, the precise utility of targeting this variable pharmacologically or by vagus nerve57 or spinal cord stimulation58 remains to be determined.

Finally, it should be emphasized that heart

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  • Cited by (0)

    Supported by grants from Center for Integration of Medicine and Innovative Technology and the National Institutes of Health.

    Dr. Verrier is an inventor of the modified moving average method for analysis of T-wave alternans, with patents assigned to Beth Israel Deaconess Medical Center and licensed by GE Healthcare, Inc. Dr. Tan declares no conflicts of interest.

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